The Los Angeles Center has made substantial contributions to the goals of CPCCRN and its growth. Our particular strengths include: 1) high enrollment in studies, 2) rich racial and ethnic mixture of children, 3) broad experience in informatics, data management and computer-based decision support (CDS) tools, and 4) unique expertise in mechanical ventilation and respiratory physiology. These make us an ideal setting for Network studies. Studies by the ARDSNet and other groups in adult patients have demonstrated that the choice of PEEP can affect mortality, both for better and worse. Little is known about methods of PEEP application in children, especially in the face of obesity and fluid overload, common problems in the PICU. The purpose of this study is to compare two Positive End-Expiratory Pressure / Inspired Oxygen (PEEP/FiO2) ventilator management strategies on optimal lung recruitment and oxygenation in infants and children with pediatric Acute Respiratory Distress Syndrome (PARDS). This has not been done previously in children. The study will compare the use of esophageal pressure recordings to individualize PEEP/FiO2 application by measuring transpulmonary pressure at end-expiration against the CPCCRN pediatric modification of the ARDS Network protocolized, population-based PEEP/FiO2 application tables. It will also address hemodynamic safety concerns by measuring cardiac output non-invasively. Computer-based Decision Support (CDS) tools already developed within CPCCRN under the leadership of the Los Angeles Center will be used in both arms. This will improve protocol adherence and ensure replicable clinical decisions for equivalent patient states to minimize confounding ventilator management variations at each clinical site. In order to overcome limitations highlighted in previous trials on PARDS, non-invasive markers of lung injury will be used both to improve patient enrollment and to characterize risk, following the guidelines of the Pediatric Acute Lung Injury Consensus Conference (PALICC). Two members of the Los Angeles Center participated in their development. We believe our concept proposal is best suited for the CPCCRN research environment as it is the only structured research environment where the detailed data and number of patients needed for this study can be obtained in a reasonable time. Moreover, the study builds upon the Los Angeles Center's previous CPCCRN research and development.